1. Field of the Invention
.alpha..sub.1 -Antitrypsin is an important protease inhibitor present in mammalian blood. Its major physiological function appears to be the inhibition of neturophil elastase, a potent protease that hydrolyzes structural proteins. It also inhibits many other serine proteases.
A low level of .alpha..sub.1 -antitrypsin in the blood is often associated with chronic obstructive pulmonary emphysema and infantile liver cirrhosis. At present, more than 30 different genetic variants have been identified. Several of these are associated with low concentrations of the inhibitor in the blood.
The normal plasma level of .alpha..sub.1 -antitrypsin is about 2 mg/ml. Under most inflammatory conditions, an acute-phase response is initiated and the concentration of .alpha..sub.1 -antitrypsin is substantially increased. In order to study .alpha..sub.1 -antitrypsin deficiency at the molecular level and examine the mechanism of the acute phase response, it would be desirable to have pure .alpha..sub.1 -antitrypsin polypeptide. The .alpha..sub.1 -antitrypsin polypeptide could be used for the formation of antibodies to the numerous determinant sites to provide for detection of variants in the blood, as a ligand in assays for .alpha..sub.1 -antitrypsin, and for introduction into a host having .alpha..sub.1 -antitrypsin deficiency.
2. Description of the Prior Art
Shochat, et al., J. Biol. Chem. (1978), 253:5630-5634; Morii, et al., J. Biochem. (1978), 83:269-277; Carrell, et al., Biochem. Biophys. Res. Conunun. (1979), 91:1032-1037 Mega, et al., Biol. Chem. (1980), 255:4057-4061; and Crawford, Arch. Blochem. Biophys. (1973), 156:215-222; have reported various characteristics of .alpha..sub.1 -antitrypsin. Kurachi, et al., Proc. Natl. Acad. Sci. U.S.A. (1981), 78:6826-6830, and Chandra, et al., Blochem. Biophys. Res. Comm. (1981), 103:751-758, describe cloning and sequencing of cDNA coding for .alpha..sub.1 -antitrypsin.